Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV

NCT05215704 | Recruiting

• 1 other identifier: NL42819.078.12
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Combination antiretroviral therapy (cART) blocks intracellular human immunodeficiency virus (HIV) replication in CD4+ T-lymphocytes, but fails to eliminate latent HIV infected CD4+ T-lymphocytes. About 7 (range \<1-100) in 106 of these cells are latently infected and can cause reactivation of proviral HIV when cART is stopped. These latently infected cells form the reservoir and must be targeted in order to cure HIV. We would like to further investigate this reservoir and assess potential interventions to eradicate it. One promising option is to further study the influence of HIV latency disruptors (latency reversing agents, LRA) on the HIV infected reservoir. These agents are used in shock and kill strategies that disrupt latency by LRA followed by the selective (induced) killing of the reservoir cell due to viro-pathogenic effects. For accurate assessment of the reservoir and potential cure strategies, including the impact of LRA on the reservoir, a large reservoir and sufficient cells for analysis are desirable. Our understanding on the reservoir comes from in vitro lymphocyte models and early ex vivo studies. Additional studies of patients with different clinical phenotypes including untreated versus treated versus the rare individuals that control HIV spontaneously are increasingly relevant to the field. Especially this last category represent biological examples of viral control without cART and are useful to study the factors that set them apart from those that need treatment for their HIV. This study aims to deepen our understanding of the HIV reservoir and cure strategies, foremost, shock and kill strategies. We will do this by setting up a durable ex vivo platform for HIV reservoir and cure studies of which the samples can be used for hypothesis generation for in-vivo studies. A project from the Erasmus MC HIV Eradication Group (EHEG).

Conditions

HIV Infections; HIV-1-infection; HIV-2 Infection

Keywords

HIV; HIV cure; HIV reservoir

Outcome Measures

Primary Outcomes (1)

• The number of HIV patients with a measurable proviral reservoir measured by molecular, flowcytometric and culture based assays

  10-15 years

Secondary Outcomes (6)

• The level of reactivation of latently HIV infected PBMCs after treatment ex vivo with established and novel HIV cure compounds (alone and in combination) as assessed by cell-associated HIVRNA.

  10-15 years

• The HIV reservoir size and activity as assessed by molecular, flowcytometric, and culture based assays ex vivo.

  10-15 years

• The HIV reservoir susceptibility to shock and kill strategies as assessed by molecular, flowcytometric, and culture based assays.

  10-15 years

• The HIV reservoir size, activity, and susceptibility to shock and kill strategies in relation to clinical phenotypes.

  10-15 years

• To measure predictive biomarkers of the size and activity of the latent HIV reservoir as assessed by molecular, flowcytometric and culture based assay ex vivo.

  10-15 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Otherwise healthy adult HIV infected patients will be recruited at the Erasmus MC outpatient clinic of infectious diseases

You may qualify if:

• Age 18 years or older.
• Confirmed HIV-1 or HIV-2 infection.

You may not qualify if:

• Inability to place 2.5 cm venous catheter or perform phlebotomy
• Major comorbidities:
• A. Severe symptomatic anemia B. Recent symptomatic cardiovascular event (unstable angina pectoris, decompensated heart failure, myocardial infarction).
• The inability to participate due to any other relevant medical, social, environmental, psychological, factors or according to the HIV treating physician's judgement

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Centre

Rotterdam, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples and leucapheresis

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Casper Rokx, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Casper Rokx, MD PhD

CONTACT

c.rokx@erasmusmc.nl

Rob Gruters, PhD

CONTACT

r.gruters@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 31, 2022
• Study Start: January 1, 2012
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

NL (1)